Effect of Drug Monitoring on Adherence and Blood Pressure: A Multicenter Randomized Clinical Trial.

BACKGROUND: Drug concentration in blood or urine is an acknowledged method to detect non-adherence. Observational studies suggest that informing patients about low or absent serum drug levels improves blood pressure (BP). We performed a multicenter randomized clinical trial to test the hypothesis that therapeutic drug monitoring (TDM) could improve drug adherence and BP in patients with uncontrolled hypertension and reduced adherence to antihypertensive drugs. METHODS: Patients were ≥18 years on stable treatment with at least two antihypertensive agents. We planned to randomize 80 non-adherent patients with a systolic daytime ambulatory BP (ABPM) ≥135 mmHg to TDM-intervention or not. The control group and the study-personnel who measured BP remained uninformed about serum drug measurements throughout. All patients and physicians were blinded for BPs. Lifestyle advice and detailed information on disease process and importance of BP treatment were given to both groups. RESULTS: From 2017 to 2022, we randomized 46 diagnosed non-adherent from a total of 606 patients with uncontrolled hypertension. The TDM-group had a 6.7 (±14.5) mmHg reduction from 147.9 (±10.3) to 141.1 (±14.1) mmHg, and the control group experienced a 7.3 (±13.2) mmHg reduction from 147.1 (±9.2) to 139.1 (±17.4) mmHg, p=0.9 between groups. Adherence improved in both groups, 73% in the TDM group and 59% in the control group became adherent at three months, p=0.51. CONCLUSIONS: In our prospective multicenter clinical trial of uncontrolled and non-adherent hypertensive patients, we found no additional effect of therapeutic drug monitoring (TDM) on blood pressure and drug adherence compared with standard care.

Evaluation of the nurse-assisted eHealth intervention 'eHealth@Hospital-2-Home' on self-care by patients with heart failure and colorectal cancer post-hospital discharge: protocol for a randomised controlled trial.

BACKGROUND: Patients with heart failure (HF) and colorectal cancer (CRC) are prone to comorbidity, a high rate of readmission, and complex healthcare needs. Self-care for people with HF and CRC after hospitalisation can be challenging, and patients may leave the hospital unprepared to self-manage their disease at home. eHealth solutions may be a beneficial tool to engage patients in self-care. METHODS: A randomised controlled trial with an embedded evaluation of intervention engagement and cost-effectiveness will be conducted to investigate the effect of eHealth intervention after hospital discharge on the self-efficacy of self-care. Eligible patients with HF or CRC will be recruited before discharge from two Norwegian university hospitals. The intervention group will use a nurse-assisted intervention-eHealth@Hospital-2-Home-for six weeks. The intervention includes remote monitoring of vital signs; patients' self-reports of symptoms, health and well-being; secure messaging between patients and hospital-based nurse navigators; and access to specific HF and CRC health-related information. The control group will receive routine care. Data collection will take place before the intervention (baseline), at the end of the intervention (Post-1), and at six months (Post-2). The primary outcome will be self-efficacy in self-care. The secondary outcomes will include measures of burden of treatment, health-related quality of life and 30- and 90-day readmissions. Sub-study analyses are planned in the HF patient population with primary outcomes of self-care behaviour and secondary outcomes of medication adherence, and readmission at 30 days, 90 days and 6 months. Patients' and nurse navigators' engagement and experiences with the eHealth intervention and cost-effectiveness will be investigated. Data will be analysed according to intention-to-treat principles. Qualitative data will be analysed using thematic analysis. DISCUSSION: This protocol will examine the effects of the eHealth@ Hospital-2-Home intervention on self-care in two prevalent patient groups, HF and CRC. It will allow the exploration of a generic framework for an eHealth intervention after hospital discharge, which could be adapted to other patient groups, upscaled, and implemented into clinical practice. TRIAL REGISTRATION: Clinical trials.gov (ID 301472).

Feasibility of telerehabilitation for heart failure patients inaccessible for outpatient rehabilitation.

AIMS: Despite strong recommendations, outpatient cardiac rehabilitation is underused in chronic heart failure (CHF) patients. Possible barriers are frailty, accessibility, and rural living, which may be overcome by telerehabilitation. We designed a randomized, controlled trial to evaluate the feasibility of a 3-month real-time, home-based telerehabilitation, high-intensity exercise programme for CHF patients who are either unable or unwilling to participate in standard outpatient cardiac rehabilitation and to explore outcomes of self-efficacy and physical fitness at 3 months post-intervention. METHODS AND RESULTS: CHF patients with reduced (≤40%), mildly reduced (41-49%), or preserved ejection fraction (≥50%) (n = 61) were randomized 1:1 to telerehabilitation or control in a prospective controlled trial. The telerehabilitation group (n = 31) received real-time, home-based, high-intensity exercise for 3 months. Inclusion criteria were (i) ≥18 years, (ii) New York Heart Association class II-III, stable on optimized medical therapy for >4 weeks, and (iii) N-terminal pro-brain natriuretic peptide >300 ng/L. All participants participated in a 2-day 'Living with heart failure' course. No other intervention beyond standard care was provided for controls. Outcome measures were adherence, adverse events, self-reported outcome measures, the general perceived self-efficacy scale, peak oxygen uptake (VO2peak ) and a 6-min walk test (6MWT). The mean age was 67.6 (11.3) years, and 18% were women. Most of the telerehabilitation group (80%) was adherent or partly adherent. No adverse events were reported during supervised exercise. Ninety-six per cent (26/27) reported that they felt safe during real-time, home-based telerehabilitation, high-intensity exercise, and 96% (24/25) reported that, after the home-based supervised telerehabilitation, they were motivated to participate in further exercise training. More than half the population (15/26) reported minor technical issues with the videoconferencing software. 6MWT distance increased significantly in the telerehabilitation group (19 m, P = 0.02), whereas a significant decrease in VO2peak (-0.72 mL/kg/min, P = 0.03) was observed in the control group. There were no significant differences between the groups in general perceived self-efficacy scale, VO2peak , and 6MWT distance after intervention or at 3 months post-intervention. CONCLUSIONS: Home-based telerehabilitation was feasible in chronic heart failure patients inaccessible for outpatient cardiac rehabilitation. Most participants were adherent when given more time and felt safe exercising at home under supervision, and no adverse events occurred. The trial suggests that telerehabilitation can increase the use of cardiac rehabilitation, but the clinical benefit of telerehabilitation must be evaluated in larger trials.

Cardiorenal syndrome and the association with fitness: Data from a telerehabilitation randomized clinical trial.

AIMS: To investigate the associations of cardiorespiratory fitness with cardiac, vascular, renal and cardiorenal characteristics in chronic heart failure in a telerehabilitation randomized clinical trial. Secondly, to evaluate the associations of cardiorenal syndrome with the effects of exercise. METHODS AND RESULTS: Sixty-nine heart failure patients attended baseline examination, and 61 patients were randomly assigned 1:1 to 3-month telerehabilitation or control. Data were collected at baseline and 3-month post-intervention, including echocardiography and vascular ultrasound, laboratory tests, exercise test with peak oxygen consumption (VO2peak ) measurement and 6-min walk test (6MWT). Baseline VO2peak and 6MWT distance was 0.85 mL*min-1 *kg-1 lower and 20 m shorter per 10 mL/min/1.73m2 lower estimated glomerular filtration rate (both P < 0.001). Heart failure patients with cardiorenal syndrome had 3.5 (1.1) mL*min-1 *kg-1 lower VO2peak and diastolic dysfunction grade 2-3, and elevated filling pressure was >50% more common compared with those without (all P < 0.05). At the 3-month post-intervention follow-up, only the non-CRS patients in the intervention group increased VO2peak (0.73 (0.51) mL*min-1 *kg-1 ), whereas VO2peak in the CRS subpopulation of controls decreased (-1.34 (0.43) mL*min-1 *kg-1 ). Cardiorenal syndrome was associated with a decrease in VO2peak in CRS patients compared with non-CRS patients, -0.91 (0.31) vs. 0.39 (0.35) mL*min-1 *kg-1 respectively, P = 0.013. CONCLUSIONS: Cardiorenal syndrome was negatively associated with VO2peak and 6MWT distance in chronic HF, and the associations were stronger than for heart failure phenotypes and other characteristics. The effect of exercise was negatively associated with cardiorenal syndrome. Exercise seems to be as important in heart failure patients with cardiorenal syndrome, and future studies should include CRS patients to reveal the most beneficial type of exercise.

A woman in her eighties with chest pain during immunotherapy for melanoma. / En kvinne i 80-årene med brystsmerter under immunterapi mot melanom.

BACKGROUND: Immunotherapy is used to treat several cancer types. As it is a relatively new type of treatment, knowledge of optimal handling of rare side effects is sparse. CASE PRESENTATION: A woman in her early eighties with inoperable metastases from malignant melanoma was given immunotherapy. Five weeks after the first dose of nivolumab 480 mg she was admitted to the hospital with symptoms of coronary artery disease. On suspicion of side effects from nivolumab, she was given prednisolone 80 mg daily. MRI of the heart showed findings highly suggestive of myocarditis. Her condition initially improved, but 9 days after leaving the hospital she developed muscular weakness and ptosis. Neurography and electromyography revealed acute axonal polyneuropathy and she was treated with mycophenolate mofetil. In the days that followed she had increasing paresis, apnoea and pain in the right shoulder. Echocardiography showed reduced systolic function. The patient died 11 days after the second hospitalisation. INTERPRETATION: The patient developed hepatitis, myocarditis and neuropathy after only one course of immunotherapy. Those are known to be rare side effects with a high mortality rate. The patient was given high dose prednisolone and mycophenolate mofetil. Intravenous immunoglobulins and/or plasmapheresis could have been alternative treatments.

Detection of Nonadherence to Antihypertensive Treatment by Measurements of Serum Drug Concentrations.

[Figure: see text].

Cardiovascular outcomes at recommended blood pressure targets in middle-aged and elderly patients with type 2 diabetes mellitus and hypertension.

PURPOSE: Available data of event-based clinical outcomes trials show that little evidence supports the guidelines recommendations to lower blood pressure (BP) to <130/80 mmHg in middle-aged and elderly people with type 2 diabetes mellitus and hypertension. We addressed this issue by post-hoc analysing the risk of cardiovascular (CV) events in mostly elderly high-risk hypertensive patients with type 2 diabetes mellitus participating in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial. MATERIAL AND METHODS: Patients (n = 5250) were divided into 4 groups according to the proportion of on-treatment visits before the occurrence of an event (<25% to ≥ 75%) in which BP was reduced to <140/90 or <130/80 mmHg. RESULTS: After adjustment for baseline demographic differences between groups, a reduction in the proportion of visits in which BP achieved <140/90 mmHg accompanied a progressive increase in the risk of CV mortality and morbidity as well as of cause-specific events such as stroke, myocardial infarction and heart failure. A progressive reduction in the proportion of visits in which BP was reduced <130/80 mmHg did not have any effect on CV risks. CONCLUSION: In mostly elderly high-risk hypertensive patients with type 2 diabetes mellitus participating in the VALUE trial, achieving more frequently BP <140/90 mmHg showed a marked protective effect on overall and all cause-specific cardiovascular outcomes. This was not the case for a more frequent achievement of the more intensive BP target, i.e. <130/80 mmHg.

Cardiovascular outcomes at recommended blood pressure targets in middle-aged and elderly patients with type 2 diabetes mellitus compared to all middle-aged and elderly hypertensive study patients with high cardiovascular risk.

PURPOSE: Event-based clinical outcome trials have shown limited evidence to support guidelines recommendations to lower blood pressure (BP) to <130/80 mmHg in middle-aged and elderly hypertensive patients with diabetes mellitus or with general high cardiovascular (CV) risk. We addressed this issue by post-hoc analysing the risk of CV events in patients who participated in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial and compared the hypertensive patients with type 2 diabetes mellitus with all high-risk hypertensive patients. MATERIALS AND METHODS: Patients were divided into 4 groups according to the proportion of on-treatment visits before the occurrence of an event (<25% to ≥75%) in which BP was reduced to <140/90 or <130/80 mmHg. Patients with diabetes mellitus (n = 5250) were compared with the entire VALUE population with high CV risk (n = 15,245). RESULTS: After adjustments for baseline differences between groups, a reduction in the proportion of visits in which BP was reduced to <140/90 mmHg, but not to <130/80 mmHg, was accompanied by a progressive increase in the risk of CV morbidity and mortality as well as stroke, myocardial infarction and heart failure in both diabetes mellitus and in all high-risk patients. Target BP <130/80 mmHg reduced stroke risk in the main population but not in the diabetes mellitus patients. Patients with diabetes mellitus had higher event rates for the primary cardiac endpoint and all-cause mortality driven by a higher rate of heart failure. CONCLUSION: In the high-risk hypertensive patients of the VALUE trial achieving more frequently BP <140/90 mmHg, but not <130/80 mmHg, showed principally the same protective effect on overall and cause-specific cardiovascular outcomes in patients with diabetes mellitus and in the general high-risk hypertensive population.

Sleepless nights and sleepy days: a qualitative study exploring the experiences of patients with chronic heart failure and newly verified sleep-disordered breathing.

BACKGROUND: Sleep-disordered breathing, including obstructive sleep apnoea and central sleep apnoea, is a common disorder among patients with chronic heart failure. Obstructive sleep apnoea is often treated with continuous positive airway pressure, but central sleep apnoea lacks a clear treatment option. Knowledge of how sleep-disordered breathing is experienced (e.g. difficulties and care needs) and handled (e.g. self-care actions) by the patients is limited, but needed, to provide patient-centred care. AIM: To explore how newly verified sleep-disordered breathing is experienced by patients with chronic heart failure. METHODS: Data were collected through semi-structured interviews and analysed with qualitative content analysis. Seventeen participants (14 men, three women), mean age 60 years (range 41-80) diagnosed with chronic heart failure and objectively verified sleep-disordered breathing (nine obstructive, seven central and one mixed) were strategically selected from heart failure outpatient clinics at two Norwegian university hospitals. RESULTS: Patients with chronic heart failure and newly verified sleep-disordered breathing (SDB) described experiences of poor sleep that had consequences for their daily life and their partners. Different self-care strategies were revealed, but they were based on 'common sense' and were not evidence-based. The awareness of having SDB was varied; for some, it gave an explanation to their trouble while others were surprised by the finding. CONCLUSION: Patients with chronic heart failure and sleep-disordered breathing experienced reduced sleep quality, influencing their daily life. Possible underlying causes of disrupted sleep, such as sleep-disordered breathing, should be identified to establish proper patient-centred treatment strategies. There is a need for new strategies to approach patients with chronic heart failure (i.e. those with central sleep apnoea) who are not subject to continuous positive airway pressure treatment for their sleep-disordered breathing.

[Congestive heart failure--etiology and diagnostic procedures]. / Kronisk hjertesvikt--etiologi og diagnostikk.

Congestive heart failure is a major health problem in the western world and the prevalence of patients with this diagnosis increases. About 2% of the adult population are affected; the majority are elderly, which represents a challenge when it comes to assessment and treatment. This article concerns the aetiology and diagnosis of congestive heart failure and provides a suggestion for guidelines. The proposed guidelines are aimed at primary, secondary and third line health care providers in Norway, and are based on previously published Norwegian guidelines and international guidelines. Hypertension and coronary artery disease account for 75-80% of known cases of congestive heart failure. The patient's history and risk factors must be investigated. Laboratory tests emphasising organ functions are important, and these should include measurement of B-type natriuretic peptide (BNP). Electrocardiograms and chest X-rays should be taken as well. All patients with suspected impaired left ventricular ejection fraction should undergo an echocardiographic examination. Invasive tests, and non-invasive imaging should be used for selected groups of patients only.

[Treatment of congestive heart failure]. / Behandling av kronisk hjertesvikt.

The Working Group on Heart Failure of the Norwegian Society of Cardiology here presents a revised programme for the treatment of congestive heart failure. Possible surgical and percutaneous interventions should be considered, and non- pharmacological measures taken as indicated for each patient. ACE-inhibitors are the first-line pharmacological therapy in heart failure with reduced left ventricular ejection fraction (< 40%). Possible adverse effects on blood pressure, renal function and electrolytes necessitate close monitoring of these variables. Beta-blockers should be considered in patients with symptomatic heart failure. If ACE-inhibitors are not tolerated, an angiotensin- II-blocker can be the added. Diuretics should only be used as adjunctive therapy to ACE-inhibitors. Aldosterone antagonists have a proven effect on survival, but close monitoring of potassium levels is imperative. Especially in the elderly, the renal function and level of electrolytes must be monitored closely. Device therapy, such ac cardiac resynchronization therapy and implantable cardioverter defibrillators, are only indicated for selected patients. ACE-inhibitors, diuretics and beta-blockers are the drugs-of-choice for patients with congestive heart failure with preserved systolic function. Health care for patients with congestive heart failure must be well organized on different levels of care and with multidisciplinary teams involved. The goal is to reduce morbidity and mortality in the heart failure population. This programme is meant for primary, secondary and third line health care providers in Norway.

[Hypertension and heart disease]. / Hypertensjon og hjertesykdom.

Hypertension commonly leads to heart disease, in particular left ventricular hypertrophy, heart failure and coronary artery disease. Left ventricular hypertrophy and coronary artery disease are both often subclinical diseases in hypertensives. Symptomatic coronary artery disease in hypertension may be due to atherosclerosis in epicardial arteries, microvascular dysfunction, reduced fibrinolytic capacity, or left ventricular hypertrophy; the latter is present in 20-50% of patients with mild to moderate and in up to 90% of patients with severe hypertension. Left ventricular hypertrophy in hypertension is associated with a twofold increase in risk of myocardial infarction, sudden death and stroke, and a fourfold increase in risk of heart failure. While coronary artery disease is the most common cause of heart failure in men, hypertension and in particular untreated isolated systolic hypertension is the most common cause in women. Heart failure symptoms may be subtle in hypertension, like tiredness or reduced physical capacity. Echocardiography can reveal subclinical heart disease as well as serve as a guide to correct diagnosis and treatment.